MiR-27a-3p Targeting GSK3β Promotes Triple-Negative Breast Cancer Proliferation and Migration Through Wnt/β-Catenin Pathway
Dysregulation of microRNAs (miRNAs) was found to play crucial roles in varieties of cancers, which affect tumor proliferation and migration. MiR-27a-3p has been identified as a tumor-related miRNA in liver cancer, lung cancer, and colorectal cancer. However, the function of miR-27a-3p in triple-nega...
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Published in | Cancer management and research Vol. 12; pp. 6241 - 6249 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
New Zealand
Dove
01.01.2020
Dove Medical Press |
Subjects | |
Online Access | Get full text |
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Summary: | Dysregulation of microRNAs (miRNAs) was found to play crucial roles in varieties of cancers, which affect tumor proliferation and migration. MiR-27a-3p has been identified as a tumor-related miRNA in liver cancer, lung cancer, and colorectal cancer. However, the function of miR-27a-3p in triple-negative breast cancer (TNBC) and its possible molecular mechanisms have still not been elucidated.
QRT-PCR technique was used to detect the expression of miR-27a-3p in TNBC and normal breast cell lines or the effects of miR-27a-3p knockdown and overexpression in TNBC cell lines. Proliferation and migration were measured by CCK-8 method, colony formation, wound healing, and Transwell assays, respectively. Furthermore, we used a dual-luciferase reporter gene assay and Western blot analysis to identify GSK3β as a target of miR-27a-3p.
In this study, we found that miR-27a-3p expression was significantly elevated in TNBC cell lines. Database analysis suggested that TNBC patients with a high expression of miR-27a-3p have poorer overall survival possibilities. Overexpression of miR-27a-3p promotes TNBC cells proliferation, colony formation, and cell migration in vitro. Nevertheless, dual-luciferase reporter result showed that miR-27a-3p directly targeted the 3'-UTR regions of GSK3β mRNA and negatively regulated its expression. Lastly, we demonstrated that miR-27a-3p inactivates Wnt/β-catenin signaling pathway via targeting GSK3β.
These results indicate that expression of miR-27a-3p was highly expressed in TNBC and promoted tumor progression through attenuating GSK3β and may have a potential molecular-targeted strategy for TNBC therapy. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1179-1322 1179-1322 |
DOI: | 10.2147/CMAR.S255419 |